大肠埃希菌感染临床资料分析和耐药相关代谢组学研究

发布时间：2018-06-22 09:58

本文选题：大肠埃希菌 + 代谢组学　；参考：《川北医学院》2015年硕士论文

【摘要】：目的:统计分析大肠埃希菌(Escherichia coli,E.coli)感染者临床资料及该菌株对三类15种抗菌药物的耐药性;用气相色谱-质谱联用(GC-MS)代谢组学的方法寻找与耐药相关的差异性代谢产物和代谢网络,并进一步探讨其与耐药之间的关系。方法:收集附属医院微生物室2012年12月至2014年10月临床非同一患者同一部位重复分离的E.coli共126株,采用琼脂二倍稀释法检测15种临床常用抗菌药物的最低抑菌浓度(minimal inhibitory concentration,MIC),并统计分析其感染者临床资料和对抗菌药物的耐药性;筛选出对上述抗菌药物全部敏感的6株(S组)和耐药谱一致的4株(R组)作为代谢组学研究对象,利用GC-MS代谢组学的方法分析S组和R组中E.coli的代谢特征谱的差异,结合相关代谢通路数据库和药物机制寻找与耐药相关的胞内差异性代谢产物和代谢网络。结果:126例患者病史资料提示平均年龄为31.57±8.26岁,女性占51.59%(65/126)。病人有基础性疾病者占10.32%(13/126),手术治疗患者占23.89%(30/126)。入院前或入院后使用2种或以上的抗菌药物治疗者占56.35%(71/126)。平均住院时间为13.6天。标本来源科室分布:泌尿科(泌尿外科和肾内科)占42.86%(54/126),普外科和肛肠科占28.57%(36/126),妇产科占14.29%(18/126),呼吸科占8.73%(11/126)。标本取材来源以尿液和粪便最多,占54.76%(69/126),其次是手术创面和泌尿生殖道分泌物26.19%(33/126),痰液11.11%(14/126)。126株E.coli对头孢唑林耐药率最高(71.43%),头孢呋辛、庆大霉素的耐药率均在60%以上,对亚胺培南/西司他丁100%敏感,头孢米诺、头孢西丁和阿米卡星敏感性均在90%以上,敏感菌株占17.46%(22/126),多重耐药(MDR)菌株占74.6%(94/126)。磷酸、丁二酸、磷酸乙醇胺、甘油、顺-10-十七碳烯酸是S组和R组的差异性代谢产物,在R组的含量均低于S组。它们参与三羧酸循环、氧化磷酸化、氨基酸代谢、磷脂代谢等代谢通路。结论:(1)我院临床分离E.coli对所试三类15种临床常用抗菌药物敏感率为17.46%,对两类抗菌药物耐药率为9.74%,多重耐药率为74.6%;亚胺培南、头孢米诺、头孢西丁和阿米卡星是治疗耐药E.coli感染的理想选择,尤以亚胺培南为最。(2)磷酸、丁二酸、磷酸乙醇胺、甘油、顺-10-十七碳烯酸是S组和R组的差异性代谢产物,它们在R组的含量皆低于S组,可能与R组中细菌在抗菌药物长期压力下的低代谢水平有关。(3)R组中丁二酸含量低可能是E.coli中TCA代谢失衡所致,进而干扰细胞的能量代谢,这大概与细菌的自我保护机制有关。(4)R组中磷酸、磷酸乙醇胺、甘油含量低可能是E.coli为逃避抗菌药物打击致使它们参与了细胞膜的空间构象改变,为其耐药性的产生提供必要的生物学基础。
[Abstract]:Objective: to analyze the clinical data of Escherichia coli (E.coli) infection and the resistance of the strain to three kinds of 15 kinds of antibiotics; to find the differential metabolites and metabolic networks related to drug resistance by gas chromatography-mass spectrometry (GC-MS), and to further explore the relationship between them and drug resistance. Methods: a total of 126 E.coli isolates from the same site in the hospital from December 2012 to October 2014 were collected, and the minimum inhibitory concentration (minimal inhibitory concentration, MIC) of 15 kinds of commonly used antibiotics was detected by agar two times dilution method, and the clinical data and antagonistic bacteria of the infected persons were analyzed and analyzed. Drug resistance; screening 6 strains (group S) and 4 strains (group R) that are all sensitive to the above antibiotics (group S) and resistance spectrum (group R). The metabolic characteristics of E.coli in group S and R group were analyzed by GC-MS metabolomics, and the related metabolic pathway database and drug mechanism were used to find the cell related to drug resistance. Results: the internal differential metabolites and metabolic networks. Results: the average age of 126 patients was 31.57 + 8.26 years, 51.59% (65/126), 10.32% (13/126) and 23.89% (30/126). 2 or more antibiotics were used before or after admission (71/126). The duration of hospitalization was 13.6 days. The distribution of specimen sources: Urology (Department of Urology and Nephrology) accounted for 42.86% (54/126), Department of general surgery and anorectal Department accounted for 28.57% (36/126), gynecologic and obstetrics accounted for 14.29% (18/126), 8.73% (11/126). The specimens were collected from urine and feces, accounting for 54.76% (69/126), followed by surgical wound and genitourinary tract. Secretion 26.19% (33/126), sputum 11.11% (14/126).126 strain E.coli was the highest (71.43%) resistant to cefazolin, and cefuroxime, gentamicin resistance rates were above 60%, imipenem / cefastatin 100%, ceftriaxone, cefoxitin and Amikacin were more sensitive than 90%, sensitive strains accounted for 17.46% (22/126), multidrug resistance (MDR). The strains accounted for 74.6% (94/126). Phosphoric acid, succinic acid, ethanolamine phosphate, glycerol, and CIS -10- seventeen carboxenoic acid were different metabolites in group S and R, and in R group were lower than that in group S. They were involved in the metabolic pathways of three carboxylic acid cycle, oxidative phosphorylation, amino acid metabolism, phospholipid metabolism, etc. conclusion: (1) the clinical separation of E.coli in our hospital on the three class 15 faces of the trial. The susceptibility rate of common antibiotics in bed was 17.46%, the rate of resistance to two types of antibiotics was 9.74%, and the rate of multidrug resistance was 74.6%. Imipenem, cephalosporin, cefoxitin and Amikacin were the ideal choice for the treatment of drug-resistant E.coli infection, especially imipenem. (2) phosphoric acid, succinic acid, ethanolamine phosphate, glycerol, and CIS -10- seventeen carbonic acid were the S group and the S group. The difference of metabolites in group R, which are lower in group R than in group S, may be related to the low metabolism level of bacteria in group R under long-term pressure of antimicrobial agents. (3) low content of succinic acid in group R may be caused by metabolic imbalance of TCA in E.coli, thereby interfering with cell energy metabolism, which is probably related to the self-protection mechanism of bacteria. (4) R group. The low content of phosphoric acid, ethanolamine phosphate and glycerin may be that E.coli is an escape from the anti antibacterial drug attack that causes them to participate in the spatial conformation change of the cell membrane, and provides the necessary biological basis for the production of its resistance.
【学位授予单位】：川北医学院
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R446.5

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